ABSTRACT: Alcohol use disorders (AUD) remain a significant problem for both women and men but stress and negative affect contribute to the initiation, maintenance of, and relapse to alcohol use in women, more so than for men. In Project 1, we will obtain preliminary data to 1) determine if guanfacine alters choice and stress-induced ethanol preference in male and female mice using a two-bottle choice drinking paradigm that is sensitive to stress, and 2) begin to determine the effects of ?2A adrenergic receptors and GABA neuron activity on ethanol-induced microglia alteration and synaptic density in female and male mice.